PB1921: IS CHEMOIMMUNOTHERAPY (CIT) HISTORY IN THE FIRST LINE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKAEMIA?
Authors: Catherine Parbutt, Talha Munir, Abraham Mullasseril Varghese
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Various phase 3 trials have demonstrated significant difference in progression free survival (PFS) for Bruton tyrosine kinase (BTKi) and BCL2 inhibitors (BCL-2i) named as targeted therapy compared to CIT and a small number have demonstrated a difference in overall survival (OS). Targeted therapy is now the standard first line treatment for patients with CLL of all ages. Studies to prove the difference in OS in real world settings are limited. Aims: Aim of the study is to assess the OS in patients who has been initiated on CIT compared to targeted therapy as first line treatment. Methods: This is a non-interventional, retrospective, observational study. Eligible subjects were adult patients with CLL who received their first line treatment between January 2010 and December 2022. All data was collected retrospectively from electronic patient records. Results: Three hundred and twenty-eight CLL/SLL patients were included in the study. Median age at initiation of treatment was 69 (range 20-97) years, 107 (32.6%) were below the age of 65 and 226 (68.9%) below the age of 75; 210 (64%) were male. Two hundred and seven (63%) patients had only one line of treatment and 121 (37%) had subsequent lines of treatment [(median 2 (range 2-8)]. Eighty-seven (26.5%) had chemoimmunotherapy alone, 98 (29.9%) had chemoimmunotherapy followed by targeted therapy on relapse and 143 (43.6%) had targeted therapy only. The first line treatments included acalabrutinib based 42(12.8%), Ibrutinib based 43(13.1%), Zanubrutinib 23(7%) venetoclax/obinituzumab 23(7%), Ibrutinib/venetoclax 9(2.7%), Idelalisib/Rituximab 6 (1.8%), fludarabine based 82(25%), chlorambucil based 60(18.3%), bendamustine based 22(6.7%), alemtuzumab based 15(4.6%) and others 3(0.9%). IGHV mutation status was checked in 196(59.8%) and 57(29.1%) were mutated, 123(62.8%) unmutated and 16(8.1%) borderline. TP53 status (deletion, mutation or both) was checked in 314(95.7%) and 70(22.3%) had TP53 mutation and/or deletion prior to first treatment. All except 3 of TP53 abnormal patients had targeted treatment or alemtuzumab as first line treatment and 2 of those 3 subsequently received targeted treatment. Median time from diagnosis to treatment initiation in chemoimmunotherapy group was 27 (range 0-234) months and targeted treatment group was 39 (range 0-432) months. Median follow up period was 81 months (95% CI 70.1-91.9). Median OS for the whole group was 114 months (95% CI 93.5-134.5). Median OS for patients who received chemoimmunotherapy alone was 58 months (95% CI 31.4-84.6), chemoimmunotherapy followed by targeted treatment at relapse was 138 months (95% CI 122.7-153.3) and targeted treatment alone was 100 months (95% CI 65.4-134.6; p=0.000). Median OS for all patients who received chemoimmunotherapy as first line treatment was 112 months (95% CI 82.9-141.1; p=0.117). Different subgroup analyses are also shown in the figure below as well as the cause of death is also shown in the figure. Summary/Conclusion: In this real word study, it has been shown that there is no OS advantage from initiating patients on targeted therapy as first line compared to chemoimmunotherapy followed by targeted therapy on relapse. This concept should be validated from multi-centric data and possibly tested in prospective trials.Keywords: B-CLL